Serum endogenous secretory RAGE level is an independent risk factor for the progression of carotid atherosclerosis in type 1 diabetes.
OBJECTIVE
Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) system plays an important role in the development of atherosclerosis. It has been recently reported that endogenous secretory RAGE (esRAGE) and total soluble RAGE (sRAGE) levels are associated with diabetic complications. The aim of the present study is to longitudinally evaluate the association between esRAGE and sRAGE levels and the progression of carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis.


RESULTS
Japanese type 1 diabetic patients (n=47, aged 24.0+/-3.1 years) were enrolled into a 4-year follow-up study and annual measurements of serum esRAGE and sRAGE levels and IMTs were performed. At baseline, mean-IMT was inversely correlated with circulating esRAGE levels (r=-0.317, p=0.0292), whereas there was not statistical significance between mean-IMT and sRAGE levels. Mean-IMT significantly increased during the follow-up period (from 0.63+/-0.10 to 0.67+/-0.10mm, p=0.0022). Annual increase in mean-IMT (=(mean-IMT after 4 years-mean-IMT at baseline)/4) was positively correlated with the arithmetic average of systolic blood pressure (r=0.310, p=0.0332) and triglyceride (r=0.337, p=0.0201), and inversely correlated with circulating esRAGE levels (r=-0.360, p=0.0124) and sRAGE levels (r=-0.406, p=0.0042) during the follow-up period. Furthermore, stepwise multivariate regression analyses revealed that continuous low levels of circulating esRAGE and sRAGE were determinants of the progression of mean-IMT independently of conventional risk factors.


CONCLUSIONS
Circulating esRAGE level as well as sRAGE level was an independent risk factor for the progression of carotid IMT in type 1 diabetic subjects.
Katakami
Naoto
N
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Suita, Osaka, Japan. katakami@medone.med.osaka-u.ac.jp
Matsuhisa
Munehide
M
Kaneto
Hideaki
H
Matsuoka
Taka-aki
TA
Sakamoto
Ken'ya
K
Yasuda
Tetsuyuki
T
Umayahara
Yutaka
Y
Kosugi
Keisuke
K
Yamasaki
Yoshimitsu
Y
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D015999:Multivariate Analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography; D055815:Young Adult
D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic